Association between systemic lupus erythematosus and myasthenia gravis: A population-based National Study
CONCLUSION: While the number of patients with both MG and SLE is small, SLE and MG are strongly associated together in very large databases and a large SLE cohort.PMID:37949200 | DOI:10.1016/j.clim.2023.109810 (Source: Clinical Immunology)
Source: Clinical Immunology - November 10, 2023 Category: Allergy & Immunology Authors: Ann Igoe Sali Merjanah Isaac T W Harley Dennis H Clark Celi Sun Kenneth M Kaufman John B Harley D C Kaelber R Hal Scofield Source Type: research
Telomere biology disorders may manifest as common variable immunodeficiency (CVID)
Clin Immunol. 2023 Nov 7:109837. doi: 10.1016/j.clim.2023.109837. Online ahead of print.ABSTRACTTelomere biology disorders (TBD) are caused by germline pathogenic variants in genes related to telomere maintenance and are characterized by critically short telomeres. In contrast to classical dyskeratosis congenita (DC), which is typically diagnosed in infancy, adult or late onset TBD frequently lack the typical DC triad and rather show variable organ manifestations and a cryptic disease course, thus complicating its diagnosis. Common variable immunodeficiency (CVID), on the other hand, is a primary antibody deficiency (PAD) ...
Source: Clinical Immunology - November 9, 2023 Category: Allergy & Immunology Authors: Benjamin Rolles Andres Caballero-Oteyza Michele Proietti Sigune Goldacker Klaus Warnatz Nadezhda Camacho-Ordonez Seraina Prader Jana Pachlopnik Schmid Margherita Vieri Susanne Isfort Robert Meyer Martin Kirschner Tim H Br ümmendorf Fabian Beier Bodo Grim Source Type: research
Telomere biology disorders may manifest as common variable immunodeficiency (CVID)
Clin Immunol. 2023 Nov 7:109837. doi: 10.1016/j.clim.2023.109837. Online ahead of print.ABSTRACTTelomere biology disorders (TBD) are caused by germline pathogenic variants in genes related to telomere maintenance and are characterized by critically short telomeres. In contrast to classical dyskeratosis congenita (DC), which is typically diagnosed in infancy, adult or late onset TBD frequently lack the typical DC triad and rather show variable organ manifestations and a cryptic disease course, thus complicating its diagnosis. Common variable immunodeficiency (CVID), on the other hand, is a primary antibody deficiency (PAD) ...
Source: Clinical Immunology - November 9, 2023 Category: Allergy & Immunology Authors: Benjamin Rolles Andres Caballero-Oteyza Michele Proietti Sigune Goldacker Klaus Warnatz Nadezhda Camacho-Ordonez Seraina Prader Jana Pachlopnik Schmid Margherita Vieri Susanne Isfort Robert Meyer Martin Kirschner Tim H Br ümmendorf Fabian Beier Bodo Grim Source Type: research
EIF2 α/ATF4 pathway enhances proliferation of mesangial cell via cyclin D1 during endoplasmic reticulum stress in IgA nephropathy
Clin Immunol. 2023 Nov 6:109840. doi: 10.1016/j.clim.2023.109840. Online ahead of print.ABSTRACTIgA nephropathy (IgAN) is an essential cause of kidney failure and end-stage kidney disease worldwide. Mesangial hypercellularity is an important characteristic of IgAN, but the underlying mechanism remains unclear. Endoplasmic reticulum (ER) stress is a series of stress responses to restore the function of endoplasmic reticulum. We aimed to explore how ER stress functioned in kidneys of IgAN. We first examined ER stress in IgAN kidneys in vivo and in vitro, by testing the levels of ER stress associated proteins (BIP, p-eIF2α a...
Source: Clinical Immunology - November 8, 2023 Category: Allergy & Immunology Authors: Zhixin Lan Lu Zhao Liang Peng Lili Wan Di Liu Chengyuan Tang Guochun Chen Yu Liu Hong Liu Source Type: research
EIF2 α/ATF4 pathway enhances proliferation of mesangial cell via cyclin D1 during endoplasmic reticulum stress in IgA nephropathy
Clin Immunol. 2023 Nov 6:109840. doi: 10.1016/j.clim.2023.109840. Online ahead of print.ABSTRACTIgA nephropathy (IgAN) is an essential cause of kidney failure and end-stage kidney disease worldwide. Mesangial hypercellularity is an important characteristic of IgAN, but the underlying mechanism remains unclear. Endoplasmic reticulum (ER) stress is a series of stress responses to restore the function of endoplasmic reticulum. We aimed to explore how ER stress functioned in kidneys of IgAN. We first examined ER stress in IgAN kidneys in vivo and in vitro, by testing the levels of ER stress associated proteins (BIP, p-eIF2α a...
Source: Clinical Immunology - November 8, 2023 Category: Allergy & Immunology Authors: Zhixin Lan Lu Zhao Liang Peng Lili Wan Di Liu Chengyuan Tang Guochun Chen Yu Liu Hong Liu Source Type: research
METTL14-m6A-FOXO3a axis regulates autophagy and inflammation in ankylosing spondylitis
In this study, we found that m6A modification was decreased in T cells of AS, and the abnormal m6A modification was attributed to the downregulation of methyltransferase-like 14 (METTL14). METTL14 exerted a critical role in regulating autophagy activity and inflammation via targeting Forkhead box O3a (FOXO3a). Mechanistically, the loss of METTL14 decreased the expression of FOXO3a, leading to the damage of autophagic flux and the aggravation of inflammation. Inversely, the forced expression of METTL14 upregulated the expression of FOXO3a, thereby activating autophagy and alleviating inflammation. Furthermore, our results r...
Source: Clinical Immunology - November 7, 2023 Category: Allergy & Immunology Authors: Yuting Chen Ye Wu Lanlan Fang Hui Zhao Shenqian Xu Zongwen Shuai Haiyang Yu Guoqi Cai He-Qin Zhan Faming Pan Source Type: research
Development of IFN β-1a versions with reduced immunogenicity and full in vitro biological activity for the treatment of multiple sclerosis
In this study, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of IFNβ-1a. Two de-immunized versions of IFNβ-1a were produced in CHO cells and designated as IFNβ-1a(VAR1) and IFNβ-1a(VAR2). First, the secondary and tertiary protein structures were analyzed by circular dichroism spectroscopy. Then, the variants were also tested for functionality. While IFNβ-1a(VAR2) showed similar in vitro antiviral activity to the original protein, IFNβ-1a(VAR1) exhibited 40% more biological potency. Finally, in vivo assays using HLA-DR transgenic mice revealed ...
Source: Clinical Immunology - November 6, 2023 Category: Allergy & Immunology Authors: Sonia Ricotti Alberto Sergio Garay Marina Etcheverrigaray Gabriel Ignacio Amadeo Anne S De Groot William Martin Eduardo F Mufarrege Source Type: research
Development of IFN β-1a versions with reduced immunogenicity and full in vitro biological activity for the treatment of multiple sclerosis
In this study, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of IFNβ-1a. Two de-immunized versions of IFNβ-1a were produced in CHO cells and designated as IFNβ-1a(VAR1) and IFNβ-1a(VAR2). First, the secondary and tertiary protein structures were analyzed by circular dichroism spectroscopy. Then, the variants were also tested for functionality. While IFNβ-1a(VAR2) showed similar in vitro antiviral activity to the original protein, IFNβ-1a(VAR1) exhibited 40% more biological potency. Finally, in vivo assays using HLA-DR transgenic mice revealed ...
Source: Clinical Immunology - November 6, 2023 Category: Allergy & Immunology Authors: Sonia Ricotti Alberto Sergio Garay Marina Etcheverrigaray Gabriel Ignacio Amadeo Anne S De Groot William Martin Eduardo F Mufarrege Source Type: research
Autoantibody subclass predominance is not driven by aberrant class switching or impaired B cell development
Clin Immunol. 2023 Nov 2:109817. doi: 10.1016/j.clim.2023.109817. Online ahead of print.ABSTRACTA subset of autoimmune diseases is characterized by predominant pathogenic IgG4 autoantibodies (IgG4-AID). Why IgG4 predominates in these disorders is unknown. We hypothesized that dysregulated B cell maturation or aberrant class switching causes overrepresentation of IgG4+ B cells and plasma cells. Therefore, we compared the B cell compartment of patients from four different IgG4-AID with two IgG1-3-AID and healthy donors, using flow cytometry. Relative subset abundance at all maturation stages was normal, except for a, possibl...
Source: Clinical Immunology - November 4, 2023 Category: Allergy & Immunology Authors: Laurent M Paardekooper Yvonne E Filli é-Grijpma Alita J van der Sluijs-Gelling Mihaela Zlei Remco van Doorn Maarten H Vermeer Manuela Paunovic Maarten J Titulaer Silv ère M van der Maarel Jacques J M van Dongen Jan J Verschuuren Maartje G Huijbers T2B c Source Type: research
Autoantibody subclass predominance is not driven by aberrant class switching or impaired B cell development
Clin Immunol. 2023 Nov 2:109817. doi: 10.1016/j.clim.2023.109817. Online ahead of print.ABSTRACTA subset of autoimmune diseases is characterized by predominant pathogenic IgG4 autoantibodies (IgG4-AID). Why IgG4 predominates in these disorders is unknown. We hypothesized that dysregulated B cell maturation or aberrant class switching causes overrepresentation of IgG4+ B cells and plasma cells. Therefore, we compared the B cell compartment of patients from four different IgG4-AID with two IgG1-3-AID and healthy donors, using flow cytometry. Relative subset abundance at all maturation stages was normal, except for a, possibl...
Source: Clinical Immunology - November 4, 2023 Category: Allergy & Immunology Authors: Laurent M Paardekooper Yvonne E Filli é-Grijpma Alita J van der Sluijs-Gelling Mihaela Zlei Remco van Doorn Maarten H Vermeer Manuela Paunovic Maarten J Titulaer Silv ère M van der Maarel Jacques J M van Dongen Jan J Verschuuren Maartje G Huijbers T2B c Source Type: research
High intestinal isoleucine is a potential risk factor for food allergy by regulating the mTOR/AKT pathway in dendritic cells
In this study, the probiotic Lactobacillus casei Zhang (LcZ) was administered to allergic individuals and the impact on allergy-related factors were determined. LcZ alleviated allergenic responses, and there was a significant correlation between the intestinal isoleucine content and IgE concentration. Metagenomics results suggest that the metabolism of the gut microbiota is a source of isoleucine. In a mouse model of food allergy, a high isoleucine diet exacerbated allergic responses and increased the activity of allergenic dendritic cell. In a dendritic cell model, a protein array revealed that the mTOR/AKT pathway mediat...
Source: Clinical Immunology - November 2, 2023 Category: Allergy & Immunology Authors: Chong Wang Yanbo Wang Fangting Wang Jiachao Zhang Zhihong Sun Heping Zhang Linglin Fu Source Type: research
DRG2 in macrophages is crucial for initial inflammatory response and protection against Listeria monocytogenes infection
Clin Immunol. 2023 Oct 31:109819. doi: 10.1016/j.clim.2023.109819. Online ahead of print.ABSTRACTInnate immune response is critical for the control of Listeria monocytogenes infection. Here, we identified developmentally regulated GTP-binding protein 2 (DRG2) in macrophages as a major regulator of the innate immune response against L. monocytogenes infection. Both whole-body DRG2 knockout (KO) mice and macrophage-specific DRG2 KO mice had low levels of IL-6 during early infection and increased susceptibility to L. monocytogenes infection. Following an initial impaired inflammatory response of macrophages upon i.p. L. monoc...
Source: Clinical Immunology - November 2, 2023 Category: Allergy & Immunology Authors: Unn Hwa Lee Sang Jin Park Seong A Ju Sang Chul Lee Byung Sam Kim Byungyong Ahn Jawoon Yi Jihwan Park Young-Wook Won In Seob Han Byung Ju Lee Wha Ja Cho Jeong Woo Park Source Type: research
In-depth immune profiling reveals advanced B- and T-cell differentiation to be associated with Th1-driven immune dysregulation in common variable immunodeficiency
Clin Immunol. 2023 Oct 31:109816. doi: 10.1016/j.clim.2023.109816. Online ahead of print.ABSTRACTCommon variable immunodeficiency (CVID) is an inborn error of immunity characterized by low levels of antibodies. In addition to infections, many patients also suffer from T-helper 1-driven immune dysregulation, which is associated with increased mortality. The aim of this study was to perform in-depth characterization of the T and the B cell compartments in a well-defined cohort of patients affected by CVID and correlate the findings to the level of clinical immune dysregulation. We used mass cytometry, targeted proteomics, fl...
Source: Clinical Immunology - November 2, 2023 Category: Allergy & Immunology Authors: Jonas Hultberg Emelie Blixt Robin G öransson J örgen Adolfsson Melissa Govender Marie Larsson Åsa Nilsdotter-Augustinsson Jan Ernerudh Sofia Nystr öm Source Type: research
High intestinal isoleucine is a potential risk factor for food allergy by regulating the mTOR/AKT pathway in dendritic cells
In this study, the probiotic Lactobacillus casei Zhang (LcZ) was administered to allergic individuals and the impact on allergy-related factors were determined. LcZ alleviated allergenic responses, and there was a significant correlation between the intestinal isoleucine content and IgE concentration. Metagenomics results suggest that the metabolism of the gut microbiota is a source of isoleucine. In a mouse model of food allergy, a high isoleucine diet exacerbated allergic responses and increased the activity of allergenic dendritic cell. In a dendritic cell model, a protein array revealed that the mTOR/AKT pathway mediat...
Source: Clinical Immunology - November 2, 2023 Category: Allergy & Immunology Authors: Chong Wang Yanbo Wang Fangting Wang Jiachao Zhang Zhihong Sun Heping Zhang Linglin Fu Source Type: research
DRG2 in macrophages is crucial for initial inflammatory response and protection against Listeria monocytogenes infection
Clin Immunol. 2023 Oct 31:109819. doi: 10.1016/j.clim.2023.109819. Online ahead of print.ABSTRACTInnate immune response is critical for the control of Listeria monocytogenes infection. Here, we identified developmentally regulated GTP-binding protein 2 (DRG2) in macrophages as a major regulator of the innate immune response against L. monocytogenes infection. Both whole-body DRG2 knockout (KO) mice and macrophage-specific DRG2 KO mice had low levels of IL-6 during early infection and increased susceptibility to L. monocytogenes infection. Following an initial impaired inflammatory response of macrophages upon i.p. L. monoc...
Source: Clinical Immunology - November 2, 2023 Category: Allergy & Immunology Authors: Unn Hwa Lee Sang Jin Park Seong A Ju Sang Chul Lee Byung Sam Kim Byungyong Ahn Jawoon Yi Jihwan Park Young-Wook Won In Seob Han Byung Ju Lee Wha Ja Cho Jeong Woo Park Source Type: research
